Experiences and perceptions of receiving and prescribing rehabilitation in adults with cystic fibrosis undergoing lung transplantation

Background Rehabilitation is prescribed to optimize fitness before lung transplantation (LTx) and facilitate post-transplant recovery. Individuals with cystic fibrosis (CF) may experience unique health issues that impact participation. Methods Patient and healthcare provider semi-structured interviews were administered to explore perceptions and experiences of rehabilitation before and after LTx in adults with CF. Interviews were analyzed via inductive thematic analysis. Results Eleven participants were interviewed between February and October 2021 (five patients, median 28 (IQR 27–29) years, one awaiting re-LTx, four following first or second LTx) and six healthcare providers. Rehabilitation was delivered both in-person and virtually using a remote monitoring App. Six key themes emerged: (i) structured exercise benefits both physical and mental health, (ii) CF-specific physiological impairments were a large barrier, (iii) supportive in-person or virtual relationships facilitated participation, (iv) CF-specific evidence and resources are needed, (v) tele-rehabilitation experiences during the COVID-19 pandemic resulted in preferences for a hybrid model and (vi) virtual platforms and clinical workflows require further optimization. There was good engagement with remote data entry alongside satisfaction with virtual support. Conclusions Structured rehabilitation provided multiple benefits and a hybrid model was preferred going forward. Future optimization of tele-rehabilitation processes and increased evidence to support exercise along the continuum of CF care are needed.


Introduction
Cystic fibrosis (CF) is a multisystem disease, primarily characterized by progressive lung disease leading to respiratory failure or referral to LTx. 1,2 Skeletal muscle impairments, reduced exercise capacity and lower levels of physical activity are also present. [3][4][5][6] There is evidence to support exercise in improving exercise capacity, pulmonary function, health-related quality and mucociliary clearance in CF. 7,8 Higher exercise capacity in LTx candidates is associated with reduced morbidity and mortality both pre-and post transplant, [9][10][11] and rehabilitation, both in the inpatient and outpatient settings is a recommended component of a LTx program. 12 Tele-rehabilitation (rehabilitation delivered over telecommunication networks and the internet) has the potential to support patients closer to home and increase access and adherence to rehabilitation. This may be particularly relevant to the CF population who are at risk of crosscolonization and infection, and have a high daily regimen of medications, nutritional management and airway clearance therapies. 13 Hospitalizations for respiratory exacerbations are common pre-LTx and can disrupt the rehabilitation program. Prior to the COVID-19 pandemic, on-site supervised rehabilitation was standard of care before and after LTx, and less was known of tele-rehabilitation in this population. Web and App-based exercise programs have been reported in three pilot studies of LTx candidates and recipients. [14][15][16] One of these studies focused solely on CF LTx candidates and found that participants who used a commercially available fitness app with asynchronous monitoring and communication completed more exercise sessions over 12 weeks than the hospital-based exercise group, although there was a high variability of completed sessions. 16 A program evaluation performed at our LTx centre following the implementation of tele-rehabilitation in 2020 in response to the COVID-19 pandemic reported good engagement despite barriers of exercise equipment, however this evaluation was not specific to LTx candidates or recipients with CF. 17 This study involved semi-structured interviews with patients and healthcare providers. The aim was to gain an in-depth understanding of the experiences and perceptions of receiving and prescribing rehabilitation care pre-LTx and in the early post-LTx period in adults with CF. Patient usage and satisfaction data from a remote monitoring App that was being utilized to support clinical outpatient care was also collected.

Study design
This study was conducted at a single Canadian LTx center (University Health Network, Toronto, Canada). Ethics approval was obtained from the research ethics board (REB #20-6015). All participants provided written informed consent that was collected remotely.

Rehabilitation delivery
For outpatients, rehabilitation during March 2020-June 2021 was delivered primarily at home with in-person sessions occurring between once a week or once a month depending on covid-19 on-site restrictions and patient stability, conditioning level, access to home exercise equipment and adherence to home exercise. There was no patient fee for in-person rehabilitation or for use of the remote monitoring App. For inpatients, in-person rehabilitation occurred at the adult CF centre pre-transplant and the transplant centre post-transplant.

Sampling and recruitment
A purposive sampling technique was utilized. Eligible participants included two groups: (i) patients aged 18 years of age or older with CF who were waiting for lung transplant (initial or re-transplant) or who underwent a lung transplant between March 2020 and June 2021 and (ii) healthcare providers at the University Health Network or its' affiliated adult CF center (Unity Health Toronto) who delivered and/ or made clinical decisions around lung transplant rehabilitation.

Informed consent process
Patients. The study lead who was also a clinician in the lung transplant program identified eligible participants. A clinician in the circle of care and not on the research team approached the patient either in-person during on-site rehabilitation or during a virtual rehabilitation visit to ask if they were willing to be contacted to learn about the study. The research assistant then called the patient to ask for permission to use their email to send the informed consent form by Institutional File Share and plan a time to call them back to discuss. Two FileShare passwords were shared verbally by phone in order to download and unzip the file. The consent process occurred through Microsoft Teams or by phone. The patient signed and returned the consent form in person, by email or via FileShare.
Providers. Providers were contacted either in-person or by email by the study lead who was a clinical colleague to tell them about the study. If interested, the research assistant sent an email with an attached consent form. The consent process occurred through Microsoft Teams or by phone. The provider signed and returned the consent form in person or by email.

Data collection procedures
Semi-structured virtual one-on-one interviews. Two interview guides (patient and provider) were developed based on a literature review, expert opinion and previous surveys that one researcher (LW) had used previously to explore perceptions of e-health interventions in solid organ transplant recipients. 18 Supplement 1S One researcher (RG) conducted the interviews in English between February and October 2021 using Microsoft Teams.
Patient usage and satisfaction data from the remote care monitoring App. An online, remote care monitoring App that was being used for clinical care since March 2020 walked people through the exercise program and allowed manual entry of the amount of exercise performed at home (e.g. frequency, intensity, time and type) and pre-and postexercise biometrics (e.g. oxygen saturation, heart rate, Borg dyspnea and leg fatigue scores). Satisfaction surveys were also sent in the App to LTx candidates after one month of using the App and to LTx recipients three months after transplant. Supplement 2S The remote care monitoring App has been described in detail elsewhere. 17

Thematic analysis
Interviews were recorded on an external digital recorder and later de-identified and transcribed verbatim. Transcripts were entered into NVIVO 12 Plus data management software. One researcher (LW) read through all transcripts and generated initial codes using an iterative-inductive analytical strategy which were organized into a coding framework. A second researcher (RG) independently applied this coding framework to one patient and one provider transcript. A meeting was held to discuss the codes and agree upon terminology which were further refined. LW reapplied this new coding framework to all transcripts and identified broad themes. Key themes were reviewed, refined and named. Both patient and provider codes were combined into the same theme were relevant, otherwise a separate theme was created.

Results
Between February and October 2021 11 people were interviewed including five patients (4 women, median age 28 (IQR 27-29) years, one awaiting re-LTx, four following first or second LTx) and six healthcare professionals (4 physiotherapists, 1 physiotherapy assistant, 1 respirologist). Participant characteristics are described in Table 1. During this time frame there were three waves of COVID-19 accompanied with varying levels of on-site ambulatory and community restrictions. 19 Patient engagement using the remote monitoring app was high with entry of home-based exercise pre-and post LTx. Table 2 All five patient participants agreed or strongly agreed that the remote patient monitoring App supported their journey in preparing for and/or recovering from surgery, empowered them to manage their health condition and provided support from their healthcare team. Six key themes were identified regarding the experience and perceptions of receiving and prescribing rehabilitation care pre-and post lung transplantation for CF. Themes along with illustrative quotes are presented in Table 3.

Theme 1-Structured exercise benefits both physical and mental health pre-and post-transplant
When working within the confines of their physiology, subject's participation in structured exercise provided physical benefits to overall conditioning, breathing and muscle strength that increased fitness for surgery and facilitated a quicker post-LTx recovery. A structured program provided clear expectations and goals that supported patients even when they weren't feeling energetic. In addition to improvements to physical functioning, patient participants felt exercise had a positive impact on their mental resilience and stamina, and that keeping themselves healthy and strong though exercise after LTx was a way to honor their donor.

Theme 2-CF-specific physiological impairments were a large barrier to exercise
Barriers to exercise focused primarily on physical impairments specific to CF with less emphasis on treatment burden or infection control. Both patient and provider participants described the multi-system presentation of CF as a barrier. In addition to symptoms common to LTx candidates such as dyspnea and fatigue, participants highlighted CF-specific impairments that limited exercise including CF respiratory exacerbations, hemoptysis, digestive issues and hospitalizations. A high daily medical regimen of airway clearance and medications was not identified by patient participants as a large barrier to exercise when at home, but rather exercise was seen as an important treatment supplement that should be part of their structured medical routine. Some participants expressed concern around infection control, however it was felt that during the COVID-19 pandemic the CF population were no longer singled out for specific isolation precautions as all LTx candidates and recipients were required to maintain physical distancing, and there was the option of home exercise.

Theme 3-Collaborative and supportive relationships, either in-person or virtual, facilitated exercise participation
Patients felt that relationships with the rehabilitation team provided oversight, accountability and allowed a tailored approach that was responsive to changes in their status and addressed other medical conditions such as nutrition and anxiety management to support exercise. This relationship was fostered both in-person and virtually using a remote patient monitoring App in the outpatient setting. In addition, the support of family and friends was very important for ongoing motivation, particularly when they would join the patient during their exercise sessions. Access to home exercise equipment and adequate space in the home was also highlighted as an important facilitator by both patients and providers. Providers felt that a 1 on 1 relationship was necessary to tailor rehabilitation, progress exercise and/or identify a deterioration of function or oxygenation. Providers who worked at the inpatient CF center stressed that their role in rehabilitation differed from the outpatient program. Specifically, their primary aim during admission of an acute CF pulmonary exacerbation was airway clearance, and rehabilitation was focused on the prevention of further deconditioning and loss of muscle mass in order to return them back to their functional baseline rather than increasing endurance and strength from baseline levels.
Theme 4-More CF-specific exercise evidence, guidance and resources are needed Patient participants felt that targeted resources and direction would have been helpful during the early stages of their condition to set expectations for lifelong exercise and physical activity. Providers felt that gaps in evidence for exercise remain, particularly in its' role for airway clearance and in the management of CF-related diabetes. It was felt Eligible/invited participants: The three physiotherapists from the adult CF centre as well as three physiotherapist assistants and three physiotherapists from the lung transplant centre who deliver outpatient rehabilitation and one physician specializing in lung transplant rehabilitation were eligible. One of the physiotherapists from the lung transplant centre was leading the research study so was therefore not invited resulting in 9 potential participants. There were 19 eligible patients. Six did not attend an in-person or a virtual rehabilitation visit during the study timeframe and therefore were not approached. 13 were approached and of these 7 did not response to or complete the virtual consent process, 1 died before consent with the remaining 5 included in the study.
that in the era of CFTR modulators, exercise may play a larger role in optimizing health-related fitness for people with a potentially different lung health trajectory, longer life expectancy and later referral for LTx.
Theme 5-Experience with tele-rehabilitation and eHealth tools during the COVID-19 pandemic resulted in preferences for a hybrid model Both patients and providers shifted rapidly to a telerehabilitation model when on-site ambulatory activity was restricted during the COVID-19 pandemic. Although patients reported that they liked the option of home exercise, they also felt that in-person rehabilitation was valuable to ensure safe and effective exercise technique and progression. Overall they preferred some flexibility to mix inperson and on-site sessions, but felt the frequency of inperson sessions should be person-specific. Providers felt that a mix of home and in-person rehabilitation was acceptable when patients had full access to exercise and monitoring equipment, where adherent to home exercise and were not experiencing a major change in their health status. However, providers felt that they could more confidently deal with emerging health changes such as exacerbations and/or increased oxygen requirements in person.

Theme 6-Virtual platforms and clinical workflows require further optimization
Provider's virtual care workflows and current eHealth tools impacted outpatient rehabilitation delivery and user experience was varied. Technology issues with connectivity and multiple communication tools that were not integrated with the electronic patient record required workarounds that increased provider workload. The large amount of data that can be collected in an App needs to be available in a summary form and/or show trends over time to be interpreted in a meaningful way that can both inform clinical care and be feasible from a workflow perspective.

Discussion
There were positive patient and provider perceptions and experiences with rehabilitation before and early after LTx in adults with CF, however further resources and evidence alongside optimization of a tele-rehabilitation or hybrid rehabilitation model is needed.
The finding that both physical and mental benefits arise from structured, regular exercise aligns with previous studies. An international survey of attitudes and experiences of physical activity sent to healthcare providers, parents/ caregivers and both pediatric and adult people with CF     would actually decrease their weight, so we work with the dietician to make sure that they're eating enough to compensate. [Provider 5] Working 1 on 1 with somebody really getting to know them, developing that relationship, and then coming up with kind of collaborative goals that you set together and then just kind of checking in with them. [Provider 1] We communicate with our psychiatry team and they assist with any antianxiety medication, that when we do see them they can do a bit more with us. [Provider 4] I really liked that [physios] could tell when you were struggling almost before you could even tell yourself. They say like "You gotta either dial it back a little bit," or in some cases patients are too scared to do, more and they'll say "Okay, let's try the next step here." So, I found that they're very in tune with the patients. Now what we're seeing is people post CFTR modulator who start taking this drug very deconditioned, then they start improving their lung function, they get they don't get sick as often, they put on 15 or 20 pounds in body weight. All of a sudden, they realize holy moly I can't do any of this stuff, not because of my lungs, but because I'm so de-conditioned that I haven't exercised.
[Provider 1] The clinic that I grew up going to, they never gave out a pamphlet on exercises to do. I remember as a kid, they promoted exercise certainly, but they never gave my parents any real guidance on exactly what exercises are best. Some instruction as to the benefits of exercise that will help expand your rib cage, get you breathing deeper could be beneficial on the pediatric side, so starting out early. [Patient 5] Beam CF platform is basically just exercise focused, so it has on demand classes, and live classes as well everyday for a variety of fitness levels, so I've recently started directing our patients to that. It's a beautiful website, it is privately owned so there is a cost associated with it, but the way I look at it is that often when patients make a financial commitment to exercise they're more likely to participate in it. It's all people either with CF or physios that are working with CF. [Provider 1] The walking or running have more bouncing effect and it actually helps them improve more sputum out of the airway. Now quite a bit of debate on whether they can actually use exercise as a way to airway clearance.  found physical, psychological and social factors were prime motives for physical activity. 20 Another online survey in adult LTx recipients with CF more than six months post-transplant found that physical activity was important for physical health and quality of life. 21 Both surveys found fatigue a common barrier to physical activity, which was also reported from both patient and provider participants in our study. Virtual relationships with healthcare providers and friends supported participant's home-based exercise program. The younger age of LTx candidates and recipients with CF may facilitate greater acceptance and usage of ehealth exercise and physical activity tools. Web-based platforms to increase physical activity have been shown to be acceptable and feasible in the CF population, with study participants also expressing preferences for a mobile App interface. [22][23][24] As remote monitoring tools, apps and wearables can accumulate significant amounts of data, ensuring appropriate clinical workflows and technical support is essential. 25 Although patient participants liked the option to exercise at home, there was also a perceived benefit for in-person sessions to safety prescribe and progress exercise. Providers felt they had more ability to assess a change in medical status in person, and some professional groups suggest that tele-rehabilitation may be less suitable for complex populations such as those with severe dyspnea, hypoxemia and recent hospitalizations. 26 Further clinical and research experience on structure and processes of emerging pulmonary rehabilitation models will inform future practice.
The patient participants in this study were a highly specialized group with CF. In order to be listed for LTx, a person has to have evidence of a support person and must agree to adhere to the medical expectations of the program in terms of mandatory rehabilitation and regular clinic visits with the multidisciplinary LTx team. Three of the five patient participants were awaiting or had undergone retransplantation. It has been reported that at the time of retransplantation LTx candidates have more renal, cardiac and pulmonary decline compared to their listing for a first transplant. 27 People listed for retransplantation may have different impairments in skeletal muscle function due to years of corticosteroid and calcineurin inhibitor use which may also impact on the volume of exercise and amount of progression they can tolerate. Their daily medical regimen may also differ in terms of medications, nutritional management and airway clearance therapies compared to when they had not undergone LTx, and thus barriers to exercise may differ.
Lastly, in the age of CFTR modulator therapy, the natural history of CF may continue to change leading to increased life expectancy and a later transition and thus older age at the time of LTx. This has implications for exercise and physical activity counselling and interventions. An increase in age-related co-morbidities such as CF-related diabetes, bone disease, cardiovascular disease and decreases in skeletal muscle mass and function may respond well to regular exercise. As exercise and physical activity is a behaviour, it is important to ensure that cardiorespiratory and musculoskeletal fitness is increased as lung function improves and weight gain occurs with CFTR modulator therapy. 28

Limitations
The sample size of patient participants was small and may not have been representative of people with different comorbidities, support networks and financial backgrounds. This study only examined one large lung transplant program with its' affiliated adult CF centre and thus the number of potential providers were limited. Over the course of this study the clinical use of CFTR modulator therapy increased at our LTx and CF centers resulting in less people with CF referred or kept on the active waiting list for LTx. This study was also performed during the COVID-19 pandemic when outpatient rehabilitation delivery was undergoing a rapid change towards tele-rehabilitation, on-site supervised activities were restricted and broad infection control mandates were present, which may have impacted perspectives around rehabilitation barriers and facilitators. Recent studies have shown that physical activity levels have been lower in people with CF during the COVID-19 pandemic due to lockdowns, closed facilities and recommended shielding. 29,30 In addition, as ambulatory outpatient visits were restricted, participants were primarily recruited and consented remotely, which may have excluded some participants who were less confident using technology in this way.

Conclusion
Structured rehabilitation is perceived as an important component of care pre-and post-LTx, with a preference for a mixed hybrid model that is optimized to meet the needs of both patients and providers. Further evidence and resources to support inpatient, outpatient and home-based rehabilitation in CF is needed.